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Bipolar Depression Research Review

Sanjay Gupta, MD
Roger McIntyre, MD, FRCPC
Released: October 28, 2021

Hospitalization Risk Among Adults with Bipolar 1 Disorder Treated with Lurasidone Versus Other Oral Atypical Antipsychotics: A Retrospective Analysis of Medicaid Claims Data

Niu X, et al. Curr Med Res Opin. 2021;37:839-846.

To compare the risk of hospitalization for an adult with bipolar I disorder treated with lurasidone vs other oral atypical antipsychotics (AAPs) as monotherapy.

A retrospective cohort study of a Multi-State Medicaid Claims database identified adults with bipolar I disorder who initiated AAPs between January 1, 2014 (index date), and June 30, 2019. Patients were continuously enrolled 12 months before and 24 months after the index date. Each month during the post–index date period was categorized as monotherapy with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone; no/minimal treatment; or other. Statistical analyses were performed to estimate hospitalization risk and length of stay (all-cause and bipolar I disorder related) compared with lurasidone.

The analysis included 8262 adults. Compared with lurasidone, odds of all-cause hospitalization were significantly higher for olanzapine and quetiapine. The risk was significantly higher for bipolar I disorder–related hospitalization for quetiapine and risperidone compared with lurasidone. The bipolar I disorder–related length of stay per 100 patient-months was more than twice as long for quetiapine vs lurasidone (8.41 vs 3.97 days, respectively).

Lurasidone-treated adult Medicaid patients with bipolar I disorder had a significantly lower risk of all-cause hospitalization than those treated with olanzapine and quetiapine and lower risk of bipolar I disorder–related hospitalization than quetiapine and risperidone. Bipolar I disorder–related hospital length of stay was significantly shorter for patients treated with lurasidone compared with quetiapine.

Clinical Commentary by Sanjay Gupta, MD
AAPs are used in 45% to 60% of patients with bipolar I disorder. There are multiple FDA-approved agents for the treatment of mania, but only 4 agents are approved for the treatment of acute bipolar depression (lurasidone, quetiapine, cariprazine, and combination olanzapine/fluoxetine). Long-acting injectables have also been FDA approved for bipolar I disorder, recognizing the lack of treatment adherence in this disease state. This is the first study comparing real-world hospitalization rates among adult Medicaid patients with bipolar I illness among those treated with lurasidone vs other atypical agents. This study substantiated the finding of a previous study in commercially insured patients and examined a 2-year time frame. We should note that this is a retrospective study, and the likelihood of a prospective study is low as the drug is approved by the FDA and such trials are expensive and difficult to conduct.

There are several limitations as claims data run the risk of misclassification and coding errors. The study focused on Medicaid patients; hence, the generalizability of the findings comes into question. The focus was on monotherapy, which is not typical for the treatment of bipolar disorder. Such patients receive an average of 3 medications. Patients on long-acting injectable were also excluded. The findings of this study are remarkable and need to be recognized by psychiatric professionals.

Clinical Insights

  • Patients with bipolar I receiving lurasidone (median dose: 40 mg/day) had lower psychiatric hospitalization rates and those who were hospitalized had a shorter duration of stay.
  • The better efficacy and tolerability of lurasidone may be associated with higher medication adherence and hence better outcomes.
  • Bipolar disorder is a lifelong condition that requires long-term treatment, and patients do have greater morbidity and lifetime depressive episodes. Lurasidone is approved by the FDA and has a favorable metabolic profile; therefore, it is a preferred choice for long-term treatment.

This study supports serious consideration of lurasidone for bipolar I disorder treatment either as monotherapy or in combination with lithium or divalproex while monitoring for akathisia, a potential adverse event and treating it with propranolol, clonazepam, or mirtazapine (in that order). Attractive features of lurasidone are its favorable metabolic profile and reduction in hospitalizations—and when hospitalizations do occur, they are of shorter durations compared with the other AAPs.

Clinical Commentary by Roger McIntyre MD, FRCPC
A paradigm shift has occurred in the conceptualization of bipolar disorder away from an episodic and acute disorder to a chronic disorder. The conceptualization of bipolar disorder as a chronic illness is also supported by economic data indicating that bipolar disorder is one of the costliest mental disorders in the United States with significant costs related to hospitalizations. The relative benefit of an FDA-approved treatment for bipolar depression in a person or the overall benefit of an FDA-approved treatment for bipolar depression includes not only evaluating efficacy and safety but also the economic implications. Medicaid is a significant provider of financing treatments for bipolar disorder, providing the impetus to evaluate the costs of the treatments of bipolar disorder as monotherapy in a Medicaid data set.

Clinical Insights

  • This Medicaid data set reminds us of the high hospitalization risk in persons with bipolar disorder during the observation period of 2014-2019.
  • Individuals treated with olanzapine or quetiapine had a significantly higher rate of hospitalizations from all causes when compared with lurasidone.
  • Treated individuals receiving quetiapine or risperidone had a significantly higher rate of psychiatric hospitalizations.
  • The reasons for the difference in hospitalization rates across agents are not known, but it can be hypothesized that it may reflect differences among agents’ intolerability (hence, adherence with treatment) and/or efficacy.

The Florida Medicaid guidelines include lurasidone as a first-line treatment option in bipolar depression because of its established efficacy safety and tolerability. The observation in this large real-world database indicates that hospitalization rates of persons with bipolar disorder receiving lurasidone monotherapy are lower when compared with other oral antipsychotics that are also approved by the FDA in bipolar disorder. The results may serve as a proxy of better tolerability and/or efficacy relative to olanzapine, quetiapine, and risperidone and should be considered by healthcare professionals as part of a multivariable set of considerations when selecting and sequencing treatments in bipolar disorder.

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